title: Advanced lung adenocarcinoma harboring a mutation of the epidermal growth factor receptor: CT findings after tyrosine kinase inhibitor therapy.
abstract: OBJECTIVE
  To study chest computed tomography (CT) in tyrosine kinase inhibitor (TKI) treatment of epidermal growth factor receptor (EGFR)-mutant adenocarcinoma.
  
  
  METHODS
  This retrospective study was approved by the institutional review board. Informed consent was waived. One hundred thirty consecutive patients with stage IV adenocarcinoma and EGFR mutations at a single tertiary center from November 2004 to April 2010 were enrolled retrospectively. CT images were analyzed with Response Evaluation Criteria in Solid Tumor guidelines. Target lesions were classified by size, type, axial location, and metastasis. Patients were followed after TKI therapy, and treatment response was classified as partial response, stable disease, or progressive disease. A Cox proportional hazards model was used to correlate baseline CT features and EGFR mutations with progression-free survival (PFS) and overall survival.
  
  
  RESULTS
  All patients underwent TKI therapy after identifying exon mutations in the EGFR gene, comprising exon 19 deletion (19del) (n = 77), L858R (n = 43), and exon 18 (n = 10). Outcomes were partial response (n = 103), stable disease (n = 22), and progressive disease (n = 5). In univariate analysis, PFS was significantly longer with small lesions (hazard ratio [HR], 1.02; 95% confidence interval [CI]: 1.01, 1.03; P < .01), nodular main lesions (HR, 0.55; 95% CI: 0.34, 0.88; P = .01), or peripheral lesions (HR, 0.62; 95% CI: 0.42, 0.93; P = .02). In univariate analysis, PFS was significantly longer with smaller lesions (HR, 1.02; 95% CI: 1.01, 1.03; P < .01), nodular main lesions (HR, 0.55; 95% CI: 0.34, 0.88; P = .01), peripheral lesions (HR, 0.62; 95% CI: 0.42, 0.93; P = .02), 19del (HR, 0.33; 95% CI: 0.14, 0.77; P = .01), or L858R (HR, 0.39; 95% CI: 0.16, 0.97; P = .04). In multivariate analysis, PFS was significantly longer with 19del (HR, 0.30; 95% CI: 0.11, 0.84; P = .02) and shorter with scattered metastases (HR, 2.25; 95% CI: 1.44, 5.51; P < .01).
  
  
  CONCLUSIONS
  Smaller nodular lesions, peripheral lesions, and 19del relate to longer PFS after EGFR TKI treatment.
authors.affiliation: From the Department of Pulmonary and Critical Care Medicine (C.M.C.), Department of Oncology (C.M.C., J.C.L.), Department of Radiology and Research Institute of Radiology (M.Y.K.), and Department of Clinical Epidemiology and Biostatistics (H.J.K.), University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Songpa-Gu, Seoul 138-736, Korea.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Choi
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Jae Cheol
authors.initials: JC
authors.lastname: Lee
authors.forename: Hwa Jung
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011857:Radiographic Image Interpretation, Computer-Assisted; D012189:Retrospective Studies; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors